Method and apparatus for creating intrauterine adhesions

ABSTRACT

An apparatus and method of use or treatment are disclosed for creating intrauterine adhesions resulting in amenorrhea. In particular, the apparatus relates to an easily deployed intrauterine implant that readily and consistently reduces or eliminates abnormal intrauterine bleeding. In addition, the apparatus is also used as a uterine marker device for visualizing endometrial tissue thickness and potential changes. The method of the present invention serves as a supplement to or a replacement for conventional hysterectomy or ablation/resection procedures used to treat menorrhagia.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] The present application claims priority of U.S. ProvisionalApplication Serial No. 60/256,529, filed Dec. 18, 2000, and U.S.Provisional Application Serial No. 60/199,736, filed Apr. 25, 2000,whose contents are fully incorporated herein by reference.

BACKGROUND OF THE INVENTION

[0002] Menstrual bleeding is a part of normal life for women. The onsetof menstruation, termed menarche, usually occurs at the age of 12 or 13.The length of a woman's monthly cycle may be irregular during the firstone to two years. Once the menstrual cycle stabilizes, a normal cyclemay range from 20 to 40 days, with 28 days commonly being an average.Age, weight, athletic activity and alcohol consumption are severalfactors that affect menstrual cycles. For example, younger women (underthe age of 21) and older women (over the age of 49) tend to have longercycle times, generally averaging 31 days and over. Similarly, women whoare very thin or athletic also have longer cycles. In contrast, womenwho consume alcohol on a regular basis tend to have shorter cycle times.

[0003] Nearly all women, at some time during their reproductive life,experience some type of menstrual disorder. These disorders range frommild to severe, often resulting in numerous lost work hours and thedisruption of personal/family life each month. In general, physicalsymptoms such as bloating, breast tenderness, severe cramping(dysmenorrhea) and slight, temporary weight gain frequently occur duringmost menstrual cycles. In addition to physical symptoms, emotionalhypersensitivity is also very common. Women report a wide range ofemotional symptoms, including depression, anxiety, anger, tension andirritability. These symptoms are worse a week or so before a woman'smenstrual period, generally resolving afterward.

[0004] Many women also suffer from a condition called menorrhagia (heavybleeding). Menorrhagia is a clinical problem characterized by extremelyheavy flow/bleeding and major discomfort characterized by blood lossexceeding 80 cc/month. It is estimated that 1 in 5 women between theages of 35 and 50, or approximately 6.4 million women in the UnitedStates alone, are affected by menorrhagia. Fibroids, hormonal imbalanceand certain drugs, such as anticoagulants and anti-inflammatorymedications, are common causes of heavy bleeding.

[0005] Women diagnosed with menorrhagia or dysmenorrhea have limitedtreatment options available to them. Currently, other than hormonetherapy and a few experimental pain management techniques, hysterectomy(removal of the uterus) and endometrial ablation/resection (destructionof the lining of the uterus) are the clinically accepted treatmentmodalities for menorrhagia. Both of these surgical procedures eliminatethe possibility of childbearing. Further, hysterectomy requires up to asix week recovery time and a lifetime of hormone therapy when theovaries are removed. Endometrial ablation has a low success rate atachieving amenorrhea (cessation of menstrual bleeding). As a result,many of the women affected by menorrhagia are driven to makelifestyle-altering decisions.

[0006] Over 600,000 hysterectomies are performed each year in the UnitedStates. It is estimated that 1 in 3 women in the U.S. have ahysterectomy before the age of 65. Menorrhagia is the most common reasonwhy hysterectomies are performed. Several studies have estimated thatmenorrhagia is the cause of 30% (some studies as high as 50%) of the600,000 annual hysterectomies, resulting in a basis of 180,000 to300,000 procedures annually. Financially, these numbers translate intoannual hospital costs that exceed $5 billion per year.

[0007] Based on these statistics, hysterectomy is a very commonoperation. In general, there are three types of hysterectomies: partial,total and radical. As shown in FIG. 1, a partial hysterectomy involvesremoval of the upper portion 10 of the uterus 12 (whereby the dottedlines in the figure indicated the area removed), leaving the cervix 14and the base 16 of the uterus 12 intact. FIG. 2 illustrates a totalhysterectomy whereby the entire uterus 12 and cervix 14 are removed. Aradical hysterectomy, shown in FIG. 3, entails removal of the uterus 12,both Fallopian tubes 18, both ovaries 20, and the upper part of thevagina 22. Each of the above three procedures may be performed via anabdominal incision (abdominal hysterectomy) or through a vaginalincision (vaginal hysterectomy).

[0008] After the operation, the hospital stay is generally less than aweek, depending on the type of hysterectomy and whether there are anycomplications. Since a hysterectomy is a major operation, discomfort andpain from the surgical incision are most pronounced during the first fewdays after surgery. Medication is available to minimize these symptoms.By the second or third day, most patients are up walking. Normalactivity can usually be resumed in four to eight weeks and sexualactivity can usually be resumed in six to eight weeks.

[0009] Since the 1800's, attempts using various treatments have beenmade to control uterine bleeding by means other than hysterectomy.Alternative methods include chemicals, steam, ionizing radiation,lasers, electrocautery, cryosurgery and others. The long-term risk forsuch procedures is quite high and may lead to other more seriouscomplications such as mixed mesodermal tumors or uterine cancer.

[0010] Typical therapy or treatment options include drug therapyfollowed by dilation and curettage (D & C) and, as a last resort,hysterectomy. Drug therapy is generally the first treatment optionemployed to treat excessive bleeding. Birth control pills, progestin,danazol and gonadotropin-releaseing hormone (GnRH) are a few examples ofdrug treatments prescribed to reduce bleeding. In general, birth controlpills contain synthetic forms of estrogen and progesterone, whichprevent ovulation and, thereby, reduce endometrial build-up orthickness. As a result, pill users normally have lighter or minimalmenstrual bleeding. Progestin, another synthetic form of progesterone,balances the effects of estrogen normally produced by the body and,similar to the pill, reduces endometrial growth. Often, Danazol andother GnRH agents are prescribed to suppress estrogen production andovulation. As a result, menstrual bleeding stops or is significantlyreduced. However, side-effects of such treatments may include bloating,breast tenderness, increased risk of osteoporosis and high cholesterol.

[0011] D & C, frequently a second treatment option for excessivebleeding, is a very common, minor surgical procedure that is generallyperformed on an outpatient basis in a hospital. Usually, the patient isgiven a general anesthetic, although the procedure occasionally isperformed using only a local anesthetic. The dilation step of theprocedure involves dilating or stretching the cervix, which is the lowerpart of the uterus. Once the cervix is appropriately dilated, thecurettage step can then be performed. During curettage, a curette (aspoon-shaped instrument) is inserted through the vagina, past the cervixand into the uterus. The curette is then used to scrape and/or collecttissue from the inside surfaces of the uterus.

[0012] Endometrial ablation has become more popular and has been offeredas another alternative treatment to hysterectomy for patients sufferingfrom menorrhagia. In 1996, 179,000 ablation procedures were performed,up from 49,000 in 1993. This technique is intended to permanently ablateall layers of the endometrium and allow the cavity to become lined withfibrous tissue.

[0013] In general, endometrial ablation is less costly and requires lessrecovery time for the patient. However, the procedure has received mixedresults for controlling bleeding, depending on the technique used, andhas a limited success rate of no greater than 20% when defined ascomplete cessation of bleeding. During one five-year study of 525 womenwith an average age of 42, endometrial ablation completely stoppeduterine bleeding only 26% to 40% of the time. However, approximately 79%to 87% of the women were satisfied with the surgery. About 16% of thewomen required a repeat ablation to stop bleeding and 9% of the womenultimately opted for a hysterectomy. Research has also shown that theeffectiveness of endometrial ablation may decline over years, withmenstruation returning in about one-third of women.

[0014] It should be noted, however, that the goal of endometrialablation was never to create amenorrhea (cessation of menstrualperiods). This procedure was originally developed as a less invasivealternative to hysterectomy in order to return women with menorrhagia toa normal menstrual flow.

[0015] In either endometrial ablation or resection, an attempt is madeto remove or destroy the entire lining of the uterus (the endometrium).Endometrial resection, first described in 1983 by De Cherney et al.,involves the use of a resectoscope-cutting loop to perform endometrialablation to remove the lining of the uterus. In contrast, ablationgenerally uses either vaporization, coagulation or some other thermalenergy source to destroy the uterine lining.

[0016] Although ablation and resection procedures are often discussed asif they are the same, they differ significantly. For example, somephysicians argue that resection is more difficult. However, when it isperformed skillfully, resection has much better results (control ofbleeding in up to 88% of patients) than roller ball ablation (40% to55%) and newer ablation techniques (3% to 30%).

[0017] There are various methods by which an endometrial ablationprocedure may be performed. These methods include roller ballelectrocautery, cryo-cauterization, microwave, free circulating water,vaporization, balloon ablation and photodynamic therapy. In general,these procedures are performed in a hospital or surgery center, not inthe physician's office, due to the need for anesthesia.

[0018] Referring to FIG. 4, conventional endometrial ablation, commonlyreferred to as “roller ball” ablation, uses a device 24 that looks likea tiny steamroller. This device 24 applies heat and, thereby, destroysendometrial tissue 26 (whereby the destroyed tissue is shown in thefigure by a dotted line) as it rolls across the uterine wall 28.Endometrial ablation usually takes 15 to 45 minutes and the patient cango home the same day, although a general anesthetic is usually required.

[0019] Another type of ablation procedure is vaporization. Thistechnique involves vaporizing uterine tissue using a thin powerful laserbeam or high electric voltage. Visualization of the uterine cavity ismade possible by filling the cavity with fluid. If any resection orcauterization is performed, a special substance, such as glycine,sorbitol or mannitol, is used so that the fluid does not conductelectricity. This prevents accidental burn injuries to the rest of theuterus. Because this procedure involves removing or destroying theendometrium using a simple, rapid technique, it is often referred to as“global” endometrial ablation.

[0020] The NovaSure System is one example of a global endometrialablation device used to perform ablation via controlled vaporization ofthe endometrium. The patient is sedated using a local anesthesia with IVsedation and the cervix is dilated. A gold-plated mesh triangle isdelivered via a slender tube and expanded into the uterus of thepatient. The shape of the mesh is configured to generally resemble theprofile of the uterine cavity. Prior to energizing the mesh, suction isapplied to bring the uterine cavity into close contact with the mesh.After energy has been delivered to the endometrial lining via the meshfor one to two minutes, the mesh is retracted and the tube removed fromthe patient's body.

[0021] In 1994, Singer et al. reported preliminary experience with anablation system incorporating an intrauterine balloon. As shown in FIG.5, balloon ablation utilizes a balloon 30 at the tip 32 of a cathetertube 34 that is filled with fluid and inflated until it conforms to thewalls of the uterus 28. A probe in the balloon (not shown) heats thefluid to destroy the endometrial lining. After eight minutes, the fluidis drained out and the balloon 30 is removed. Pregnancy is possible ifsome of the lining is maintained, but the risk to mother and child isconsiderable.

[0022] Photodynamic therapy is another type of ablation method. Alight-sensitive agent (photofrin II) that contains a cell-killingsubstance is given intravenously and is absorbed by the endometrium. Alight anesthetic is administered and the physician then inserts a smallprobe into the uterine cavity, through which laser light is transmittedfor a few minutes. The light activates the photofrin II, which causesdestruction of the endometrium. Early results show reduced bleedingwithout significant side effects.

[0023] Other ablation methods to treat menorrhagia, such as microwaveand freezing (cryoablation) techniques, are currently beinginvestigated. However, long-term studies using these treatments todetermine their effectiveness at producing amenorrhea and any potentialside effects are still needed.

[0024] Although ablation and resection procedures are less invasive thanhysterectomies, there are various complications that may occur. Examplesof possible complications include perforation of the uterus, injury tothe intestine, hemorrhage or infection. Another concern associated withablation treatment involves the risk of cancer. Since ablation does notremove the uterus, women still are at risk for developing endometrialcancer (although the risk is reduced; however, no clinical proof iscurrently available). Further, because endometrial ablation alters thewall of the uterus, early detection of cancerous changes may bedifficult to identify.

[0025] Other potential side effects of ablation procedures areinfections caused by ablation or similar procedures and intrauterineadhesions. Intrauterine adhesions or synechiae are described as scartissue inside the uterine cavity. Termed Asherman's Syndrome,intrauterine adhesions 36, as shown in FIG. 6, are band-like formationsthat develop as a result of injury or trauma to the uterus 12 (due to,for example over-vigorous curettage to the uterus 12) or can also happensimultaneously.

[0026] In 1894, Heinrich Fritsch was the first to describe amenorrhearesulting from traumatic obliteration of the uterine cavity followingpuerperal curettage. However, it was not until 1948, that knowledgeabout uterine adhesions was first disseminated in medical journals byJoseph G. Asherman, for whom the condition is named. In 1957, the17^(th) Congress of the Federation of French Speaking Societies ofGynecology and Obstetrics proposed the following classification ofuterine synechiae:

[0027] Traumatic Synechiae connected with surgical or obstetricalevacuation of the uterus

[0028] Spontaneous synechiae of tuberculosis origin

[0029] Synechiae occurring after myomectomy

[0030] Synechiae secondary to the attack of chemical or physical agentsand likewise those resulting from atrophic changes

[0031] In general, two types of traumatic synechiae are currentlyrecognized. The first type is stenosis or obliteration of the cervicalcanal. The second type of traumatic synechiae is partial or completeobliteration of the uterine cavity by conglutination of the opposingwalls.

[0032] Other terms, such as endometrial sclerosis, traumatic uterineatrophy, uterine artesia, uterine synechiae and adhesive endometriosis,have also been used to describe the phenomena of Asherman's Syndrome.The severity of adhesion is generally classified into one of thefollowing three groups or classes: Class I represents adhesionsoccurring in less than one-third of the uterine cavity with both ostia(i.e. openings of the Fallopian tubes) visible; Class II representsadhesions occurring in one-third to one-half of the uterine cavity withone ostium visible; and Class III represents adhesions occurring ingreater than one-half of the uterine cavity with no ostium visible.

[0033] Although Asherman's Syndrome has been studied extensively andnumerous articles and papers have been written on the topic, uncertaintystill exists as to the predominant causative factor(s) and biologicalmechanism(s). A general diagram illustrating the process of adhesionformation after trauma is illustrated in FIG. 7. It is believed that ifthe endometrium is severely damaged, it may be replaced by granulationtissue. When this happens, the opposing uterine walls adhere to oneanother and form scar tissue. In particular, adhesions form andtransluminally bridge the anterior and posterior surfaces of the uterus.The adhesions or tissue that is formed between the walls comprisesconnective tissue that is, typically, avascular. Soon after, the tissuemay be infiltrated by myometrial cells and, later, covered byendometrium.

[0034] Conventionally, intrauterine adhesions have been regarded asundesirable conditions (for example U.S. Pat. No. 6,211,217, issued toSpinale et al, U.S. Pat. No. 6,136,333, issued to Cohn et al. and U.S.Pat. No. 6,090,997, issued to Goldbert et al.). Indeed, in several knowntreatment methods for menorrhagia, it has been encouraged to avoid thecreation of adhesions. Even in those circumstances where clinicians haveexperimented with adhesion formation, the results have not provedpromising. For example, in the March 1977 edition of the Israel Journalof Medicine, an article by J. G. Schenker, entitled Induction ofIntrauterine Adhesions in Experimental Animals and Women, described anexperiment in which surgical sponges were implanted into thesubcutaneous wall of the patient. The sponges remained in thesubcutaneous wall until fibroblasts, or connective-tissue cells, wereformed within the sponges. Next, the sponges were then removed andimplanted into the uterus of the same patient.

[0035] Schenker observed that, after a period of time, adhesions wereformed in the areas adjacent to the location of the implanted fibroblastbearing sponge. No adhesions were observed in areas that did not havecontact with the fibroblast bearing sponge. These experiments werecarried out in several animal models (for example, rabbit, rat andprimates) and humans. Schenker concluded that it was possible toartificially create adhesions within the uterus, but that such aprocedure was not practical.

[0036] In view of the above, there is a need for a minimally invasivedevice and method to treat abnormal intrauterine bleeding. Inparticular, it is desirable that the device have a high success rate attreating menorrhagia and have minimal to no side-effects or relatedcomplications. Such a device must also be biocompatible and non-toxic.In addition, the related treatment methods should reduce patientrecovery times and hospital costs. Overall, the method of treatmentshould also improve the quality of life for patients.

BRIEF SUMMARY OF THE INVENTION

[0037] In general, the present invention contemplates an implantabledevice for treating excessive bleeding in a body cavity. The devicecomprises a biocompatible material that is deliverable into the bodycavity. The biocompatible material contains an attribute that promotestissue growth that results in adhesion formation within the body cavity.The attribute of the biocompatible material is defined by at least oneof a mechanical component of the biocompatible material and anon-cultured biologic component of the biocompatible material.

[0038] The present invention also contemplates a method of creatingadhesions in a body cavity. In general, the method comprises insertingan implantable device within the body cavity. The method also includeslocating the implantable device at an optimal site within the bodycavity, wherein the optimal site promotes effective adhesion formationto control bleeding.

[0039] The present invention further contemplates a pretreatment devicefor creating trauma to a tissue within a body cavity. The pretreatmentdevice generally includes a stem section and a trauma-inducing sectionadjacent to the stem section. In another embodiment, the pretreatmentdevice comprises a pretreatment fluid and a flexible tube housed withina catheter and used to insult the tissue with the pretreatment fluid.

[0040] The present invention also contemplates a method ofcontraception. In general, the method comprises inserting an implantabledevice within a uterus and locating the device at an optimal site withinthe uterus. The optimal site promotes adhesion formation and preventsconception.

[0041] In addition, the present invention also contemplates a tool usedto deploy an implantable device within a uterus. In one embodiment, thetool comprises a cervical cap and a guide located on a proximal end ofthe cervical cap. In an alternate embodiment, the tool comprises one ormore expanding elements attached to the implantable device and one ormore manipulator elements. In another embodiment, the tool is used todeploy an implantable device and comprises a guide directed forplacement of the implantable device within the uterus to createadhesions.

[0042] The present invention also contemplates a device for monitoringthe tissue of a uterus comprising at least one imagable marker. Themarker has a size that is less than a size of an unexpanded uterus and asurface for adhering the marker to a uterine wall. In addition, themarker is composed of a biocompatible material suitable for permanentimplantation is the uterus.

[0043] The present invention also contemplates method of monitoringtissue of the uterus comprising introducing at least one imagable markerinto the interior of the uterus and allowing the at least one marker tobecome embedded in tissue formed on the interior of the uterus. Themethod also includes using the at least one marker as a referencelocation to evaluate tissue features on the interior of the uterus. Inaddition, the at least one imagable marker is introduced into theinterior during a procedure wherein the uterus is being treated for acondition of menorrhagia. Alternatively, the method may also include atleast two imagable markers that are introduced into the uterus andwherein the at least two imagable markers provide a two dimensionalframe of reference.

BRIEF DESCRIPTION OF THE DRAWIINGS

[0044] Other features and advantages of the present invention will beseen as the following description of particular embodiments progressesin conjunction with the drawings, in which:

[0045]FIG. 1 is a sectional view of an embodiment of a hysterectomy;

[0046]FIG. 2 is a sectional view of another embodiment of ahysterectomy;

[0047]FIG. 3 is a sectional view of yet another embodiment of ahysterectomy;

[0048]FIG. 4 is a perspective view of one embodiment of an ablationprocedure;

[0049]FIG. 5 is a perspective view of another embodiment of an ablationprocedure;

[0050]FIG. 6 is a perspective view illustrating intrauterine adhesionsassociated with Asherman's Syndrome;

[0051]FIG. 7 is a general diagram illustrating the process of adhesionformation;

[0052]FIG. 8 is a perspective view of an embodiment of the intrauterineimplant device in accordance with the present invention;

[0053]FIG. 9A is a front perspective view of a uterine cavity in anon-distended state;

[0054]FIG. 9B is a side perspective view of a uterine cavity in anon-distended state;

[0055]FIG. 10 is a perspective view of an embodiment of the intrauterineimplant device in accordance with the present invention;

[0056]FIG. 11 is a perspective view illustrating an embodiment of arandom fiber bundle in accordance with the present invention;

[0057] FIGS. 12A-12F illustrate various embodiments of a pretreatmentdevice in accordance with the present invention;

[0058] FIGS. 13A-13C illustrate alternate embodiments of a pretreatmentdevice in accordance with the present invention;

[0059] FIGS. 14A-14C illustrate various views of another embodiment of apretreatment device in accordance with the present invention;

[0060]FIG. 15 illustrates a sectional view of another embodiment of apretreatment device in accordance with the present invention;

[0061] FIGS. 16A-16D illustrate various views of a cervical cap usedwith a delivery tool in accordance with an embodiment of the presentinvention;

[0062]FIG. 17 illustrates a perspective view of the distal end of acatheter in accordance with an embodiment of the present invention;

[0063] FIGS. 18A-18B illustrate an embodiment of the deployment tool inaccordance with the present invention;

[0064] FIGS. 19A-19B illustrate another embodiment of the deploymenttool in accordance with the present invention;

[0065] FIGS. 20A-20B illustrate yet another embodiment of the deploymenttool in accordance with the present invention;

[0066]FIGS. 21A and 21B illustrate another embodiment of the deploymenttool in accordance with the present invention;

[0067] FIGS. 22A-22B illustrate perspective views of embodiments of aself-deploying implant structure in accordance with the presentinvention;

[0068]FIG. 23 illustrates an alternate embodiment of the implant inaccordance with the present invention;

[0069]FIG. 24 illustrates another embodiment of the implant inaccordance with the present invention;

[0070]FIG. 25 illustrates an embodiment of a deployment device andimplant in accordance with the present invention;

[0071]FIG. 26 shows an alternate embodiment of a deployment device andimplant in accordance with the present invention;

[0072]FIG. 27 illustrates an alternate embodiment of the implant inaccordance with the present invention;

[0073] FIGS. 28A-28C illustrate an embodiment of a catheter used inaccordance with the present invention;

[0074]FIG. 29 shows another embodiment of the im plant in accordancewith the present invention;

[0075] FIGS. 30A-30C illustrate an alternate embodiment of a deploymenttool in accordance with the present invention;

[0076] FIGS. 31A-31B illustrate an embodiment of a tool used inaccordance with the present invention;

[0077]FIG. 32 shows an embodiment of a marker in accordance with thepresent invention;

[0078]FIG. 33 shown an alternate embodiment of a marker in accordancewith the present invention; and

[0079]FIG. 34 illustrates a perspective view of an implanted marker inaccordance with an embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0080] Referring to FIG. 8, an embodiment of the intrauterine implantdevice 40 in accordance with the present invention is shown deployedwithin a uterus 42. The uterus 42, or womb, is part of the femaleinternal genitals. The uterus 42 is a hollow, muscular organapproximately four inches long and three inches wide and is generallyshaped like an upside-down pear. It should be noted that the uterus 42depicted in FIG. 8 is in a distended state to clearly show the uterinecavity 44. However, it is understood that the uterine cavity is normallyin a collapsed state, as shown in FIGS. 9A and 9B.

[0081] Two openings 46 located at the upper end of the uterus 42 lead tothe Fallopian tubes that are connected to the ovaries (not shown).Opposite to the upper end openings 42 is a lower, narrow open end 48that forms the cervix 50 of the uterus 42 and extends to the vagina 52.The thick walls of the uterus 42 are comprised of three layers of tissueand muscle: the inner endometrial layer, the middle myometrial layer andthe outer perimetrial layer. It is the inner endometrial layer or liningthat separates from the uterus 42 and leaves the body as the menstrualflow during a woman's menstrual period.

[0082] Excessive menstrual flow or bleeding, termed menorrhagia, isindicative of abnormal sloughing of the endometrial tissue layer. Unlikeconventional therapies such as hysterectomy or ablation/resectionprocedures, as described above, the device 40 of the present inventionachieves amenorrhea (i.e. cessation of bleeding) by way of an implant orsubstance that promotes formation of intrauterine adhesions. Theintrauterine adhesions cause cessation of bleeding by a deactivation ofthe endometrial tissue, due to possibly a pressure gradient orneuro-modulating effect. Occlusion or obliteration of the uterine cavitymay result. It is important to note that the endometrial tissue isdeactivated through means other than the direct destruction of thelining, and that endometrial deactivation has been seen even in thepresence of a small number of adhesions.

[0083] In general, the device of the present invention comprises abiocompatible material that is deliverable within a body cavity, such asthe uterus. The material contains an attribute promoting tissue growththat results in adhesion formation within the body cavity. The attributemay be defined by a mechanical component and/or a non-cultured biologiccomponent, further described below. Although the invention as disclosedherein generally refers to a uterus, other body cavities, such ascavities within a heart, abdomen or other similar cavities, are alsoincluded within the scope of the present invention.

[0084] As shown in FIGS. 8 and 10, one embodiment of the device 40 ofthe present invention comprises a sterile material generally shaped orhaving physical properties to conform to the internal structure of theuterine cavity 44. In general, the device material may be flexible,rigid or semi-rigid and sized to fit within the uterus 42 of a patient.As such, the device 40 should be more or less triangularly shaped,having a height, X, of approximately 7 inches (17.78 cm) and a base, Y,of approximately 4 inches (10.16 cm). In an alternate embodiment (notshown), the device 40 comprises a flowable liquid or material thatconforms to the uterine anatomy following device delivery.

[0085] Device Materials

[0086] The device 40 of the present invention can be made from a widevariety of materials including, but not limited to, mesh, suture, gel,porous, allograft, protein, hydrogel, liquid sealant, glue, cellulose,alginate, tissue, kitosan, particulate, foam and any combination ofmaterials. The properties or characteristics of these materials may benon-absorbable, temporary/absorbable, whereby the material is brokendown by the body through any means including enzymatic, hydrolytic,mechanical, etc. and excreted, or permanent/resorbable, whereby thematerial is remodeled through some process to form host or other similartissue. In addition, the device material should be biocompatible,non-toxic and, preferably, one that is approved/cleared by the Food andDrug Administration (FDA) and has been used for a long period of time inhumans with the purpose of creating adhesions. Further, for embodimentsof the device 40 having a mechanical configuration, it is desirable thatthe material be capable of conforming to irregular volumes and/orshapes. In general, the device 40 should be designed such that it can beplaced in, stored in and deployed from a catheter or similar devicedelivery tool.

[0087] In one embodiment, the material is a woven, surgical mesh.Alternatively, the mesh can be braided, spun, knitted, non-woven and anystructural combination thereof. Examples of representative surgicalmeshes include GORE-TEX® (manufactured by W.L. Gore & Associates,Arizona), Marlex® (manufactured by C. R. Bard, New Jersey), Mersilene®(manufactured by Johnson & Johnson, New Jersey), Prolene® (manufacturedby Johnson & Johnson, New Jersey), Surgipro® (manufactured by USSurgical, Connecticut), Surgisis® (manufactured by SIS Technology CookGroup, Indiana), Vicryl® (manufactured by Johnson & Johnson, New Jersey)and Atrium Surgical Mesh (manufactured by Atrium, New Hampshire).Specific references for these materials may be found in themanufactures' product catalogues. Additional surgical mesh materialssuch as polyester, felt, polyethylene fiber, non-absorbable mesh, PTFE(Polytetrafluoroethylene), absorbable mesh and other mesh materials notspecifically disclosed herein may also be used to create or enhance thedevelopment of intrauterine adhesions 36.

[0088] In general, these materials are typically used for creation ofadhesions or tissue repair within other regions of the body. One exampleof such use is hernia repair, whereby a specialized mesh or screen isused to hold the hernia in place. For this application, the materialacts like a plug and soon becomes incorporated by the surrounding tissueto strengthen the weakened area.

[0089] Although select literature references describe some of thematerials as being adhesion barriers, these materials are in fact verygood at creating adhesions under specific circumstances. One suchexample is Surgicel® oxidized regenerated cellulose (manufactured byJohnson & Johnson, New Jersey), which is considered an adhesion barriermaterial and, in certain circumstances, an adhesion creator/promoter.Therefore, both adhesion barrier and adhesion promoter materials may beused for the device 40 of the present invention.

[0090] In another embodiment of the invention, the implant 40 is made ofa woven material, such as a fabric with a specific weave, that is alsobiocompatible. In this configuration, the material of the device createsa lattice-like structure (having openings or pores) that promotesinfiltration of fibrous tissue, resulting in adhesions 36. The materialmay be metallic, polymeric or a bio-material (including combinations ofmaterials) and can be absorbable or non-absorbable, depending on thephysical and procedural requirements. Additional material specificationsor variables may include type of weave (such as plain, open, closed,twill, dutch, reverse dutch, twill dutch, or taffeta, includingcombinations of weaves), mesh count, fiber diameter, filament type (suchas monofilament fiber or multi-filament fiber) or whether there areinterconnection of weave points. A reference containing additionalspecifications, variables and general information on woven materials isSefar America, Inc., Depew, New York (sales literature booklet, dated1998), which is incorporated herein by reference.

[0091] Alternatively, the device 40 of the present invention can also bemade of non-woven materials. One type of non-woven material is a randomfiber bundle 54. The fiber bundle 54 may be a thin mat, similar to awoven mesh, with an irregular fiber pattern. Examples of materialshaving an irregular fiber pattern include Scotchbrite® or Brillo® padmaterials. In addition, the material may be fabricated from anymonofilament or multi-filament material. An example of a monofilamentmaterial that can be used for the implant is suture material, such asProlene® or Vicryl® (manufactured by Johnson & Johnson, New Jersey).Although the fibers of the non-woven material are arranged in a randomorientation, the configuration of the fibers produces an associatedeffective pore size 56, shown in FIG. 11. Additional examples ofnon-woven materials include all the materials listed above, sincematerials fabricated into a woven product can also be manufactured intoa random fiber bundle 54.

[0092] Numerous manufacturing methods and associated techniques may beused to fabricate the woven and non-woven materials used in the device40 of the present invention. For example, in one embodiment, amonofilament having a thickness within the range of 0.003 to 0.007 inch(0.00762 cm to 0.01778 cm) is cut into 0.118 inch to 0.197 inch (0.3 cmto 0.5 cm) segments. The segments are then shaped into a predeterminedconfiguration, such as a sphere or a cube. The porous individual shapesare then arranged into the final material design. The porosity of theresultant material is dependent on the size and shape of the fibers andthe amount of compression (density) of the fibers. Examples of othermanufacturing techniques within the scope of the present disclosureinclude heating, ultrasonic cutting, cold cutting, ultrasonic welding,injection molding, compression molding, stamping, drawing, forming andother techniques not specifically disclosed, but well known in the art.

[0093] In another embodiment, the device 40 of the present invention ismade of porous materials. Examples of such porous materials include, butare not limited to, ceramics, alumina, silicon, powdered metals,Nitinol®, stainless steel, titanium, porous polymers, such aspolypropylene, polyethylene, acetal, nylon, polyester, and anycombination of such materials. Although these materials (and others notspecifically described, but included in the scope of the claimedinvention) may not be inherently porous, various manufacturing andprocessing techniques may be used to give the materials selectiveporosity characteristics.

[0094] In addition, one or more of these materials may be furtherincorporated into a mesh matrix (i.e. porous fibers woven into a mesh orconfigured in a random orientation). Alternatively, the materials can beconfigured as many particles of equal or different size or shape thatare constructed into a matrix. In another embodiment, the polymericmaterials may be manufactured to form a sponge-like material with openpore cells. This sponge-like configuration not only promotes adhesions36, but also allows the implant 40 to better conform to the internalarea of the uterine cavity 44. Specific examples of such materialsinclude Ivalon, a polyvinyl sponge (manufactured by C. R. Bard, NewJersey) and Surgifoam® (manufactured by Johnson & Johnson, New Jersey).However, it should be noted that other materials not specifically listedherein may also be used.

[0095] Both the size of the pores of the material as well as thematerial's physical characteristics have an impact on the effectivenessof the implant 40. These material attributes determine the type oftissue that will develop or grow into the mesh and, ultimately; the typeof adhesion 36 that will form within the uterus 42. The directcorrelation between these parameters for treatment of menorrhagia can bedetermined from existing material classifications or types based ontissue in-growth, such as those used for hernia repair. For example,Type I includes materials with pore sizes greater than 75 microns whichallows for growth of macrophages, fibroblasts (fibroplasias), bloodvessels (angiogenisis) and collagen fibers into the pores. This poresize is similar to the pore sizes found in Prolene® (manufactured byJohnson & Johnson, New Jersey), Marlex® (manufactured by C. R. Bard, NewJersey) and other meshes described above. As such, Type I materials aresuitable device materials.

[0096] Type II materials are micro-porous meshes with pore sizes lessthan 10 microns in at least one of three dimensions. Materials such asGORE-TEXD (manufactured by W.L. Gore & Associates, Arizona), PTFE andother surgical membranes are typical examples of these meshes. Thus,Type II materials are also appropriate device materials.

[0097] Type III materials contain multi-filaments and includemacro-porous and/or micro-porous components. In general, Type IIImaterials have varying pore sizes and are a combination of Type I andType II materials. Several examples of Type III materials include Dacronmesh (such as Mersilene®, manufactured by Johnson & Johnson, NewJersey), braided polypropylene mesh (such as Surgipro®, manufactured byUS Surgical, Connecticut), and perforated PTFE (such as GORE-TEX®MYCROMESH®, manufactured by W.L. Gore & Associates, Arizona). These andother Type III materials not specifically listed herein may also be usedfor the device 40 of the present invention.

[0098] In another embodiment of the invention, the device or implant 40is fabricated from a liquid sealant or glue, such as collagen,tissue/collagen, thrombin, polymer, fibrin-based sealants and anycombination thereof. In general, these materials are typicallyconfigured in a liquid format. However, collagen is a very commonsubstance and may be found in numerous configurations, including flour,compressed mat pad, non-woven fiber or other molded, extruded orcompressed shapes with varying density and/or porosity. Examples ofcollagen and tissue/collagen materials contemplated herein includeAvitene® (manufactured by C. R. Bard, New Jersey), Helitene®(manufactured by Integra LifeSciences Corporation, New Jersey),Dermalogen®, Dermaplant™ (manufactured by Collagenesis, Inc,Massachusetts), Apligraf®, Engineered Collagen Matrix™ and Vitrix™(manufactured by Organogenesis Inc., Massachusetts). The collagen may besynthesized or derived from bovine, porcine or human sources.

[0099] An example of a collagen-thrombin sealant is Costasis®.Costasis®, manufactured by Cohesion Technologies, California, is acollagen-thrombin composite for use as a hemostatic agent to arrest orcontrol bleeding at various sites within the patient's body. Thismaterial is comprised of bovine fibrillar collagen and bovine thrombinsuspended in calcium chloride. At the time of application, fibrinogen(taken, for example, from the patient's plasma) is mixed with theCostasis®, thereby providing fibrinogen that is cleaved by the thrombinto form a collagen-reinforced liquid hemostat. The resultant liquidmaterial may then be applied to the target site to control bleeding.

[0100] Alternatively, the physical properties of the liquid sealants maybe altered to create hemostatic solids of specific shapes or pliablegeometries. In one embodiment, the sealant material may be placed in acarrier matrix that has specific flow requirements and may be activatedby heat or moisture to change the sealant's physical characteristics. Anexample of an appropriate carrier matrix is thrombin-based CoStop®, alsomanufactured by Cohesion Technologies, California. However, unlikeCostasis®, CoStop® does not require plasma from the patient. Simplycombining the patient's blood with the thrombin-based CoStop® issufficient to cause platelet activation. As soon as the combination ofblood and thrombin causes platelet activation, the thrombin furthercatalyzes the mixture to form a fibrin clot. As such, plateletactivation initiates clot formation. A collagen-fibrin matrix develops,forming the basis or support-structure for the tissue that will becreated at the target site. Thus, when used to treat menorrhagia,CoStop® is placed within the uterus 42 of the patient and forms thecollagen-fibrin matrix. The newly formed tissue bridges together theposterior and anterior walls of the uterus 42, thereby creating anadhesion 36 and promoting amenorrhea.

[0101] Alternative methods and components may also be used to modify thephysical properties of the liquid sealants. Although not specificallymentioned herein, these methods and components are well known in theapplicable art and, therefore, are within the scope of the presentdisclosure and claimed invention.

[0102] In another embodiment, the device 40 of the present invention ismade of allograft materials (i.e. a graft of tissue taken from a donorof the same species as the recipient). These materials use the structureand properties of the allograft tissue as a matrix for new tissueformation. Osteofil™ (manufactured by Regeneration Technologies Inc.,Florida) is an example of one such material. The Osteofil® is placedwithin the uterus 42 of the patient and a fibrous tissue is formedwithin the matrix. This new tissue forms the basis for the adhesion 36.The allograft tissue from Regeneration Technologies Inc. is initiallycontemplated as de-mineralized bone; however, other tissues derived fromanimals or humans may also be used. In addition to Osteofil®, othersimilar materials including, but not limited to, Natural Matrix(Xenograft), such as OsteoGraf® N-Block (manufactured by Cera MedDental, LLC, Colorado) and other tissues available from variousaccredited tissue banks are also within the scope of the claimedinvention.

[0103] In yet another embodiment, protein materials are used tofabricate the device 40 of the present invention. Various companies andorganizations have studied the use of proteins for creating bothnon-stick and attachable surfaces. One such company is Protein PolymerTechnology located in San Diego, Calif. Protein Polymer Technologycreates synthetic genes using recombinant DNA technology. In particular,Protein Polymer Technology is able to configure small protein buildingblocks into high molecular weight polymers.

[0104] Another company that uses proprietary technology to createapplication specific proteins is Gel-Del Technologies (St. Paul, Minn.).Gel-Del Technologies, like Protein Polymer Technology, and other similarcompanies process proteins using various methods. The physical structureand composition of the protein are modified to create a wide variety ofproperties for the protein. For example, proteins have been created thathave cellular receptors, which promote active association or adhesion36. The physical characteristics (for example, shape) of the protein andits side chain elements influence the development of a fibrous responseand the formation of the desired adhesions 36. In particular, theavailable side chain elements regulate selective infiltration of tissueinto the protein structure, thereby producing adhesions 36 at the tissuetarget site.

[0105] In general, proteins may be developed into a wide variety offormats. Examples of various protein formats include small beads,sheets, strips or other regular or irregular shaped configurations. Theprotein format allows the protein to be implanted in, for example, theuterus 42 to create the response necessary for adhesion formation.

[0106] In another embodiment of the invention, the device or implant 40is fabricated from hydrogel materials. Hydrogels are coherentthree-dimensional polymeric networks that can absorb large quantities ofwater without dissolution of the polymer network. Classes of hydrogels,based on their method of preparation, include homopolymer hydrogels,copolymer hydrogels, multipolymer hydrogels and interpenetratinghydrogels. In general, hydrogels are hydrophilic polymers incorporatingChitson derivatives or polyethylenimine together withpolyvinylpyrrolidone (PVP). Hydrogels may also include cellulosederivatives, polyvinyl alcohol (PVA) or polyethylene glycol (PEG). Anexample of one common hydrogel is polyHEMA (poly(2-hydroxyethyl)methacrylate) These highly compatible water-soluble polymer systemsnaturally combine with each other to form gels possessing excellentphysical properties. These properties may be varied by the chemistriesof the gel (i.e. compounding), active ingredients and biomolecules,which can be readily incorporated without impairing biological activity.Virtually any material that can be dissolved, emulsified, or suspendedcan be added prior to gel-formation and evenly distributed in thefinished gel.

[0107] The hydrogel Aquatrix™ II (manufactured by Hydromer, New Jersey)is an example of one such hydrogel product. The gel may be loaded withany of the above-mentioned materials, such as Marlex® (manufactured byC. R. Bard, New Jersey), Mersilene® (manufactured by Johnson & Johnson,New Jersey), Surgipro® (manufactured by US Surgical, Connecticut),Surgisis® (manufactured by SIS Technology Cook Group, or any othermaterial that is pulverized, ground, etc. and combined with the hydrogelmaterial. In this configuration, the hydrogel is acting as a carriermaterial to allow for dispensing of the scaffold or lattice material.The material can then be delivered as a flowable liquid with asuspension of particles. Further, the gel may be formulated to beabsorbed or resorbed by the body within 30 to 60 days. However, theparticle/mesh would remain, forming the desired adhesion 36 at thetarget site. In an alternate embodiment, the gel may be formulated to benon-absorbable. In the case of a non-absorbable gel, the gel may beplaced at the target site and then blown with a gas to form small pores.The pores function in a manner similar to the mesh openings or pores,allowing in-growth of tissue and, ultimately, forming adhesions 36.

[0108] In general, the materials used with the device 40 of the presentinvention may be comprised of a combination of absorbable and/ornon-absorbable materials or components. In one embodiment, theabsorbable material may be comprised of a radio-opaque marker, or anyother type of imagable marker, that allows the target site to be imaged.In another embodiment, the absorbable material may be used to fixate thenon-absorbable material at the target site in the patient. For example,the absorbable material may be configured as a cervical cap. Thecervical cap is inserted at the time of implantation of the device 40and holds the device 40 in-place within the uterus 42. Withinapproximately 8 weeks, adhesions 36 form and the body of the patientabsorbs the absorbable material of the device 40.

[0109] Method of Use

[0110] Many methods for creating intrauterine adhesions 36 arecontemplated herein. Each methodology has a slightly different mechanismfor creating adhesions 36. As explained above, only a limitedunderstanding of the actual mechanism for adhesion creation is currentlyknown. However, it seems that intrauterine adhesions 36 perform the samefunction of producing amenorrhea.

[0111] In one embodiment, the size and/or configuration of the device 40is optimized to promote effective adhesion development within the uterus42. In another embodiment, the device 40 is configured to contactsubstantially the entire area of the endometrium to maximize the yield(i.e. up to 100% coverage) of adhesions within the uterus 42.Alternatively, there may be optimal locations within the uterus 42 forsite-specific deployment and/or placement of the device 40. As such, theimplant 40 need only contact specific or discrete areas of theendometrium for effective adhesion formation (i.e. adhesions in lessthan 100% of the endometrium). For example, the device 30 may be locatedin the cervical canal, and not the uterus 42, to produce sufficientadhesions 36 to control bleeding. As another example, the device 40 maybe positioned at a specific site only within the uterus 42.Alternatively, a combination of uteral and cervical locations may beused for beneficial adhesion formation.

[0112] In another embodiment of the invention, the implant or device 40may include a means for assessing and determining specific areas in theuterus 42 that are areas of excessive bleeding. These discrete areas maythen be treated to specifically form adhesions 36 at these target sites.This approach allows the endometrium to remain viable and,simultaneously, reduces and/or controls bleeding. Since the endometriumis not completely obliterated, this method may allow for reversal of theprocedure (i.e. removal of adhesions). Research has shown that adhesions36 may be removed and, thus, uterine viability restored.

[0113] In general, the method of use or treatment system of the presentinvention is contraceptive in nature. The device or implant 40 createsintrauterine adhesions 36 which deactivate the endometrial tissue. Inaddition, the adhesions 36 may also obstruct the Fallopian tubes and/orthe entrance to the Fallopian tubes. This, in turn, eliminates thepossibility of pregnancy (i.e. prevents conception) and childbearing.However, if only a limited area within the uterus 42 requires formationof adhesions 36, the procedure and its associated effects may bereversed. Therefore, if the adhesions 36 are not extensive, it ispossible to restore menstrual function, and the potential of pregnancy,to the uterus.

[0114] Adhesion formation or coverage is important not only in placementof the coverage (which is related to device placement) but alsopercentage of coverage. Although the device 40 and methods referencedherein are directed at creating 100% coverage of adhesions 36 over theentire area of the endometrium, it should be understood that alternativedevice configurations and methods of use relating to less than 100%adhesion and/or endometrial area coverage are also contemplated herein.For example, in general, the percent of coverage must be greater than75% and/or the placement of coverage should be within the lowertwo-thirds of the uterus and/or the entire cervical canal. Othercoverage options, though not specifically described herein, are alsoincluded within the scope of the claimed invention.

[0115] The general adhesion formation is a localized response to aninflammatory condition and foreign body (i.e. intrauterine device 40).The curettage or other pretreatment (further discussed below) causestrauma to the endometrium and initiates an inflammatory response. Thebody then begins to create fibroblasts (connective tissue) at the injurysight as means to heal the trauma). These fibroblasts continue torespond to the localized inflammation creating more and more fibroustissue. As the fibrous tissues are created, the posterior and anteriorwalls of the uterus 42 are joined more closely by the scar tissue. Themyometrial cells eventually infiltrate the scar tissue and thesurrounding tissue reabsorbs the endometrium. Long-term deactivation ofthe endometrial tissue is believed to be due in part to the increasedintrauterine pressure created by the adhesions 36. There are also othermodulating factors, not specifically described herein, that maycontribute to the deactivation of the endometrium.

[0116] In addition to creating permanent intrauterine adhesions 36 andtreating menorrhagia, the intrauterine device 40 of the presentinvention can also be used on a temporary basis or as a lifestylechoice. The disclosed implant device/system 40 could also offer womenthe option of whether or not to have periods. Thus, the device 40 may beused as a convenience to women to end their menstrual periods withouthaving to undergo major surgery. Further, the device 40 may be used toeliminate painful menstrual cycles or premenstrual symptoms. As yetanother alternative, the device 40 may be used as a temporary means ofcontraception. When a woman is ready to have children, the procedurecould be reversed, whereby the adhesions 36 are removed and menstruationreturns.

[0117] Pretreatment

[0118] In one embodiment of the invention, the methodology used tocreate adhesions 36 involves pretreatment of the endometrium prior toplacement of the device 40 in the uterus 42. The pretreatment method maybe either direct or indirect. Generally, indirect pretreatment occursduring the time period prior to the procedure. In contrast, directpretreatment occurs during the actual procedure.

[0119] Direct pretreatment (via mechanical means, chemical means or acombination thereof is performed in order to invoke a healing responsefrom the uterus 42. One type of direct pretreatment involves creatingtrauma to the endometrium prior to deployment of the device 40. Methodsto achieve this trauma and, in some instances, necrosis of tissue mayinclude curettage or a form of endometrial ablation. These methods maybe performed with a sharp or blunt curette (vacuum curettage), rollerball electrocautery device, thermal energy device (such asre-circulating hot water), hot water filled balloon, radio-frequency(RF) energy director, microwave, cryogenic device (to freeze thetissue), cytotoxic agent, intense LASER light and other devices capableof imparting trauma to the endometrial lining, including combinations ofsuch devices.

[0120] One embodiment of a pretreatment device 60 in accordance with thepresent invention is shown in FIGS. 12A and 12B. The pretreatment device60 is configured similar to that of a bottle-brush and can also functionas the implant. In this configuration, the pretreatment device 60includes a stem section 62 and an adjacent trauma-inducing section 64consisting of bristles or spike-like projections. The stem 62 of thedevice may be made of rigid polymers, ABS, nylon, PVC, metallics, suchas stainless steel or aluminum, and any combination of such materials.The bristles 64 can be fabricated from semi-rigid polymers, nylon orpolyethylene. Alternatively, the trauma-inducing section 64 can beconfigured as a Brillo® pad-like structure 66 capable of scouringtissue, as shown in FIG. 12C. The Brillo® portion 66 may be comprised ofcollagen coated with a sclerosing agent and can self-expand whendeployed from the catheter 68.

[0121] Prior to delivery, the brush or bristle portion 64 of the device60 is contained in the distal section 70 of a catheter or other similartype of delivery tool 68. Preferably, the outer surface of the deliverytool 68 is smooth and/or lubricious to allow for easy insertion into thepatient. During the delivery and treatment procedure, the delivery tool68 is inserted transcervically into the patient and the distal section70 is positioned within the uterus 42. The pretreatment device 60 ismaneuvered so that the bristle portion 64 of the device 60 is deployedat the target site. The device 60 is further manipulated, for example,rolled, twisted, pushed and/or pulled, so that the brush portion 64inflames the endometrium tissue. The brush portion 64 is thendisconnected from the pretreatment device 60 and left in the uterus 42of the patient. The bristles 64 of the device 60 allow in-growth offibrous tissue and promote adhesion formation. After the implant 40 isdeployed, the catheter 68 is removed from the patient.

[0122]FIG. 12D illustrates an alternate embodiment of the bottle-brushpretreatment device 60. The distal section 70 of the device 60 comprisesa multiple-pronged brush 72. This configuration reduces the amount ofmanipulation required to produce sufficient trauma to the tissue and,also, allows for greater coverage of the endometrium.

[0123] In yet another embodiment of the bottle-brush pretreatment device60, the distal section 70 of the device 60 includes a wire with sharpprotrusions 74, similar to a barbed-wire, as shown in FIG. 12E. As withthe bottle-brush configuration, the barbed-wire end 74 of thepretreatment device 60 is rolled, twisted, pushed and/or pulled acrossthe surface of the tissue to cause sufficient insult to the endometrium.Alternatively, an electric current can be applied to the wire 74 asanother means of further abrading the endometrial tissue.

[0124] Referring to FIG. 12F, the bottle-brush portion of thepretreatment device-60 can also be designed in a cap or collagen plug 76configuration. The collagen plug 76 has a naturally abrasive surface andis attached to a stylet 78 for manipulation and deployment. The stylet78 is rotated, pushed or pulled to create sufficient trauma to theendometrium. Alternatively, a crystalline material could be embedded inthe collagen of the plug 76 to create greater surface roughness. Afterthe pretreatment procedure is complete, the plug 76 is unscrewed fromstylet 78 and remains in the uterus 42 to promote adhesion formation.

[0125] Referring to FIGS. 13A and 13B, an alternate embodiment of thepretreatment device 60 comprises a wire-formed distal end 80. The distalsection of the device 60 is comprised of one or more wires 82 that areconfigured to form an egg-beater or whisk-like design. Nitinol®,stainless steel, titanium and other similar materials, includingcombinations of such materials, may be used to fabricate the wires 82 ofthe device 60. Prior to insertion through the cervix 50 and into theuterus 42 of the patient, the wires 82 are retracted into the cannula 68of the delivery tool. The wires 82 may fold together, similar to closingan umbrella, or twist toward the center axis of the device 60, as shownin FIG. 13C, in order to fit within the cannula 68. After the device 60is positioned within the uterus 42, the wire-formed distal end 80 isdeployed causing the wire form to radially expand from the center axisof the device 60. The device 60 is then manipulated in a curettage-likeaction to scrape or insult the endometrium. After the pretreatmentprocedure is complete, the wire-formed distal end 80 is retracted andthe device 60 is removed from the patient.

[0126] In another embodiment of the invention, a balloon 84 having arough external surface is used to induce trauma to the endometrium. Asshown in FIGS. 14A and 14B, the balloon 84 is deflated and housed withinthe lumen of a cannula 68 prior to deployment. After the distal portionof the pretreatment device 60 is accurately positioned within the uterus42, the balloon 84 is deployed or radially inflated to fill the uterinecavity. The external surface of the balloon 84, shown in FIG. 14C, mayinclude various fine wires, blades, small bristles or other abrasivetextures capable of abrading tissue. The device 60 is then manipulated,for example, rotated, pushed and/or pulled, or repeatedly inflated anddeflated, so that the abrasive surface of the balloon 84 inflames theendometrium. The balloon 84 is deflated and retracted into the cannula68 and the device 60 is removed from the uterus 42 of the patient afterthe pretreatment procedure is completed.

[0127] Referring to FIG. 15, the pretreatment device 60 of thisembodiment of the invention utilizes a type of “sandblasting” or liquidabrasion technique to create trauma to or insult the endometrium. Aflexible tube 86 having a curved, steerable tip housed within a catheter68 is used to deliver the pretreatment fluid 88 and, thereby, insult thetissue. In one embodiment, the fluid 88 comprises a crystalline saltthat is suspended in or pulled into the water stream. Prior to delivery,the uterus 42 of the patient may be distended utilizing a gas, such ascarbon dioxide (CO₂), or a mechanical spreader to fully expose theentire surface area of the endometrium. The pretreatment device 60 isthen inserted through the cervix 50 and into the uterus 42 of thepatient. After the device 60 is properly located in the uterus 42, thesteerable tip is maneuvered within the uterus 42 so that the fluidsuspension 88 impinges on the endometrium and blasts away the tissue.The pretreatment device 60 is removed from the patient after theprocedure is completed. Although a flexible tube having a curved,steerable tip housed within a catheter is one embodiment, other tubeand/or catheter configurations and steering/guiding means, though notspecifically described herein, are also included within the scope of theclaimed invention.

[0128] Indirect pretreatment involves the use of drugs or the patient'sown biological timing cycle. In one embodiment, a hormonal drug therapyis used to help reduce the thickness of the endometrium and downregulate the patient prior to the procedure. Drugs such as depolupron(luprolide acetate) may be used to stimulate such a response when givenin dosages of 3.75 gm/month. This drug therapy may be initiated up tosixty (60) days prior to receiving the device 40. In addition, thistreatment may continue for a period post-implant to ensure completeacceptance of the device 40 at the target site. Alternatively, otherhormone-altering medications (such as progesterone, estrogen),antibiotics, drugs or other indirect pretreatment preparations may alsobe used prior to implantation of the device 40 within the patient'suterus 42.

[0129] In an alternate embodiment, indirect pretreatment involves timingthe device implantation procedure to the patient's normal menstrualcycle. For example, for some patient's, optimal timing is defined as thepoint in time when the patient's endometrium is in a specific state orcondition. Generally, the endometrium is at its thinnest at thebeginning and end of the menstrual cycle. In particular, the fourth orfifth day after the initiation of bleeding is known to be when theendometrium is at its thinnest and beginning to reform (i.e. also knownas the proliferative stage). As such, the endometrium is most vulnerableto insult and should be in an optimal state for adhesion formation.Therefore, it would be most advantageous to perform the procedure usingthe intrauterine device 40 of the present invention during these timeperiods. In addition, timing could also be used in conjunction with drugtherapy to further optimize the endometrial lining.

[0130] Another embodiment of a pretreatment method uses drugs, hormonesor other chemicals either alone or in conjunction with the mechanicalpretreatment devices 40 previously disclosed. For example, themechanical devices 40 may be coated with the chemicals configured in adry format. The chemicals are hydrolyzed and, thereby, activated whenthey come in contact with the patient's body fluids and/or tissues.Alternatively, the chemical(s) may be dispensed in a liquid format atthe treatment site and allowed to act upon the tissue for a specifiedtime period. At the end of the time period, the implant may be deployedor, as an alternative, the reaction is stopped prior to the implantbeing deployed.

[0131] Examples of appropriate chemicals include weak acids, weak bases,saline (with a high concentration of salt to create an osmotic effect),silver nitrate, quinine solution, sodium morrhuate, sodium tetrade,alcohols, alcohols with formalin (i.e. formaldehyde) and other similarscterosing/necrosing agents or chemicals that cause insult to theendometrium. This pretreatment procedure may also require post-procedureneutralization of the chemicals followed by a lavage of the uterinecavity to allow proper adhesion formation.

[0132] Post-Treatment

[0133] After the device 40 is implanted at the target site in thepatient's uterus 42, the patient may be placed on antibiotics to treatpossible infections that may occur within the uterus 42. Although it maynot be desirable to eliminate a low grade infection since this may beone of the factors that allows for the successful creation of uterineadhesions, long-term unresolved infections are undesirable and should betreated. Alternatively, additional hormone therapy, drugs or chemicalsmay also be given to the patient as post-treatment (to down regulate thepatient) or for a prescribed period of time after the procedure.

[0134] Method of Device Deployment

[0135] The preferred method for deployment of the device 40 of thepresent invention is trans-vaginally and trans-cervically, without theneed for surgical intervention, and, therefore, can be performedaseptically. In general, a catheter, cannula or similar device 68 isinserted through the cervix 50 and into the uterus 42 of the patient. Afluid, gas or mechanical means may be used to distend the uterus 42,thereby facilitating delivery of the device 40. The device or implant 40is then deployed through the catheter 68 with or without the use ofadditional tools, out the distal end of the catheter 68, and into theuterine cavity 44. After device delivery, the catheter 68 is removedfrom the patient and the uterus 42 is subsequently allowed to contractor collapse to its natural state, whereby all of the uterine walls-arebrought into contact with the device 40. In most cases, the procedure isperformed without the use of a hysteroscope or other imaging device.Thus, the procedure is performed without direct visualization of theuterine cavity. However, if necessary, imaging techniques such asultrasound and fluoroscopy may be used. In general, the procedure of thepresent invention allows the patient to be treated in an out-patientsetting and requires minimal pain management and time.

[0136] In an alternate embodiment, an additional apparatus or tool isused with the implant 40 of the present invention. The additionalapparatus is a hollow tube or guide that forms a pathway to the cervix50. The guide is implanted, either permanently or temporarily, withinthe patient. Alternatively, the apparatus may also be a lumen, channelor other similarly configured component. The pathway formed by theapparatus not only enables easy insertion of the device 40 but alsoallows for drainage of the uterine cavity 44. In addition, the pathwaymay also be used for post-procedure therapy or future diagnosis of theuterine cavity 44. For example, if required, a biopsy of the uterinetissue may be performed using the channel as an access port.

[0137] Alternatively, a cervical cap can also be used in conjunctionwith a deployment or delivery tool. As shown in FIGS. 16A and 16B, thecervical cap 90 comprises a one-way valve device 92 that is deployed onthe cervix 50 of the patient. In addition to the one-way valve 92, thecap 90 also includes a hollow tube or guide 94 located on the proximalend of the cap. In the embodiment shown in FIG. 16A, the guide 94 allowsaccess for a tool, such as a catheter 96. Initially, the cap 90 isinstalled on the catheter/delivery tool 96. One or more slits 98 locatedon the valve or duck-bill portion of the cap 90 open to allow passage ofthe catheter 96 there-through, as shown in FIG. 16C. When the catheter96 is inserted through the cervix 50 and into the uterus 42 of thepatient, the cap 90 is deployed onto the cervix 50. After the implant 40is delivered and the catheter 96 removed from the uterus 42, the cap 90remains attached to the cervix 50.

[0138] In an alternate embodiment, the cervical cap forms a cup-shapeddevice 100 attached to a hollow tube or catheter body 96. Referring toFIG. 16D, the cup 100 attaches to the cervix 50 of the patient (notshown) and includes one or more lumen/ports for dispensing fluid,creating vacuum, delivering tools (such as a curret wire) and deployingthe implant. In addition, the deployment tool may also be configured toinclude a speculum 102 to dilate the vagina and allow free movementthere-through of the catheter portion of the tool.

[0139] In another embodiment of the present invention, device deploymentis conducted via a cannula or catheter 96 inserted through the vaginalopening and the cervix 50. The cannula provides a means of access to theinside of the uterus 42. As shown in FIG. 17, the distal end 104 of thecannula or catheter 96 comprises an atraumatic, blunt tip 106. The tip106 is made of a low durometer material, such as silicone, low durometerPVC, polyurethane, thermoplastic elastomers (TPEs) or other materialscomprising a shore hardness of less than 50 durometers. In order towithstand insertion forces, the body of the catheter 96 is made ofhigher durometer materials, such as Polyvinyl Chloride (PVC),Polypropylene, urethane, polyethylene or other similar materials. Usingthis access means, the physician can then dispense the material ordeploy the device 40 using either direct mechanical motion (styletmovement) or pressure/force created in a device external to the patient(for example, a syringe or spray-can type device).

[0140] Numerous methods for dispensing various types of implants 40 maybe used in conjunction with the cannula or catheter 96. For example, inone embodiment, the intrauterine device 40 is comprised of a mesh sheetthat is cut to a predetermined size. Basing the dimensions on a largepopulation sample can be used to optimize dimensions of the implantsize. Alternatively, the mesh sheet can be custom sized to the patient'suterus 42 by pre-imaging the uterus to determine its shape and thenusing that image to cut the mesh into the appropriate configuration. Themesh sheet is loaded into the cannula 96 and the cannula 96 ismanipulated through the cervix 50 and into the uterus 42. A stylet, wireor other type of tool is used to push the mesh out of the cannula 96 andinto the uterine cavity. The mesh unfolds, due to either physicianmanipulation or the material characteristics of the mesh, and covers theposterior surface of the uterine cavity.

[0141] Several embodiments of various deployment tools are shown in thefollowing Figures. In general, the deployment tools include one or moreexpanding elements attached to the implant. The expanding elements maybe absorbable, resorbable or non-absorbable. In the non-absorbableconfiguration, the expanding elements are detached from the implantafter deployment and removed from the patient. The expanding elementsare generally attached to the implant in such a way as to cause theimplant to unfold, spread and/or expand within the body cavity. Inaddition, one or more manipulator elements can also be used to motivate,urge or manipulate the expanding elements into a configuration thatstretches and expands the implant within the body cavity. Themanipulator elements may also be absorbable, resorbable ornon-absorbable.

[0142] Referring to FIGS. 18A and 18B, one embodiment of the deploymenttool comprises a wire hook 110 and one or more wires 108 that areattached to the implant 40 via a one-way barb 109. During deployment ofthe device 40, the barbed-wires 108 are advanced through the distal end104 of the catheter 96 and into the uterus 42 of the patient. Thewire-hook 110 is then retracted causing the implant 40 to expand andspread into the uterine cavity. In general, the barbed-wires 108 aredesigned and fabricated to expand into a fan-shape when extended fromthe catheter lumen. However, the particular location of attachment ofthe barbed-wires 108 to the mesh material also promotes furtherstretching or expansion of the implant 40 in both vertical andhorizontal directions. After the implant 40 is properly positioned inthe uterus 42, the wire-hook 110 is advanced and used to release thebarbed-wires 108 from the implant 40 and retract the wires 108 back intothe lumen of the catheter 96 for subsequent removal from the patient.

[0143] Another embodiment of a deployment tool is shown in FIGS. 19A and19B. The deployment tool and delivery method of this embodiment aresimilar to that of an intrauterine device (IUD). The deployment toolcomprises a catheter 96 and three rigid lumens or arms 112 that areattached to the implant 40. For an implant 40 configured similar to aninverted triangle, two of the lumens or arms 112 a are attached to equalhalves of the base 114 of the triangularly-shaped implant 40 and thethird lumen 112 b is attached to and runs along the height 116 of thetriangularly-shaped implant 40. A string or monofilament 118 is housedwithin the lumen and attached to the outer end 120 of each of the arms112 a. The strings 118 are threaded through the lumen that runs alongthe height 116 of the implant 40 and into the catheter 96 formanipulation by the physician. Prior to delivery, the arms 112 a areretracted adjacent to the third lumen 112 b. After the tool is insertedthrough the cervix 50 and into the uterus 42, the three rigid lumens 112are positioned within the uterine cavity using a stylet or similardevice. The strings 118 are pulled by the physician in a proximaldirection, thereby causing the arms 112 a to deploy the implant 40.After the device 40 is implanted in the uterus 42, the catheter 96 isremoved from the patient. The biocompatible lumens 112 and strings 118remain in the uterus 42 and/or are absorbed by the tissues.

[0144] In an alternate embodiment (not shown), a hinge located at thejunction of the three lumens 112 replaces the function of themonofilament 118. In this configuration, the hinge, in a spring-likefashion, automatically deploys the arms 112 a of the tool as soon asthey are released from the catheter 96 into the uterus 42 of thepatient. This configuration and method is also similar to the IUD designand method of deployment.

[0145] Referring to FIGS. 20A and 20B, the deployment tool comprises anelastic membrane 122, such as a balloon, coated with mesh, meshparticulate or other adhesion creating substance 124. The substance 124forms a brittle coating on the external surface of the membrane 122.During deployment, the catheter 96 is placed in the uterus 42 of thepatient and the balloon 122 is advanced and inflated via an inflationlumen. The expanded membrane 122 causes the particulate 124 to break offthe surface of the balloon 122 and coat the endometrium. The balloon 122is then deflated and removed from the uterus 42 of the patient.Alternatively, the balloon 122 can be made of a biocompatible materialand, therefore, can remain within the uterine cavity.

[0146] Another embodiment of the deployment tool of the presentinvention is shown in FIGS. 21A and 21B. The deployment tool comprises acatheter 96 and an inflatable tube 126 attached to the perimeter of thedevice or implant 40. The inflatable tube 126 includes an inflationlumen 128 that is connected to the tube 126 and runs along the length ofthe catheter 96. The device 40 is deployed in the uterine cavity 44according to the above-described methods. The tube 126 is then inflated,causing the implant 40 to conform to the internal geometry of theuterus. The tube 126 may either be sealed (at its connection 130 withthe inflation lumen 128) or disconnected from the inflation lumen 128 bytwisting the catheter 96. Therefore, the tube portion 126 of thedeployment tool remains in the uterus 42 in either an inflated ordeflated state.

[0147] Alternatively, the implant 40 may have a self-expanding structureattached to its perimeter to motivate it to unfold. This structure mayconsist of a material that has a memory and/or spring-like structure orbehavior (i.e. elastic properties). Examples of representative materialsinclude, but are not limited to, metallics, such as Nitinol® orstainless steel, and polymerics, such as nylon, acetal or propylene.

[0148] In one embodiment, shown in FIG. 22A, the self-deployingstructure is a wire 132 that is attached to a portion of the perimeterof the implant 40. The wire 132 is made of a thermally activatedmaterial, such as Nitinol®, that expands in response to the patient'sbody temperature. Alternatively, the frame of the device comprises avery compliant, tightly wound spring 134. Referring to FIG. 22B, thewire diameter of the device, d, is approximately 0.001 inch (0.025 cm)and the spring diameter, D, is about 0.010 inch 0.25 cm). However, otherspring configurations may also be used with the present invention. Thegarter-like spring 134 self-expands upon deployment from the catheter 96and spreads the device 40 within the uterine cavity.

[0149] In an alternate embodiment, shown in FIG. 23, a spring 136,located near the base 138 of the implant 40, forces the wire frame 140of the device 40 into an expanded configuration after the device 40 isdeployed from the catheter 96. In yet another embodiment, the wire frame142 of the device 40 includes a pivot point 144 near its base. Referringto FIG. 24, in this configuration, the wire frame 142 forms an“X”-shaped device 40, with the mesh 146 attached to the upper-half ofthe “X” and the spring 148 attached to the opposite, lower half of the“X.” As in the previous embodiment, after the device 40 is deployed fromthe catheter 96, the spring 148 forces the lower half of the frame 142to expand, consequently forcing the upper half to also expand. This, inturn, causes the mesh portion 146 of the device 40 to evenly spreadwithin the uterine cavity.

[0150] In an alternate embodiment, the device 40 is comprised of meshstrips 150 cut into small, thin rectangles, ovals or other variousshapes. The mesh strips 150 are loaded into the cannula 96 and deployedby the physician in a manner similar to those described above. Theconfiguration of the device 40 together with the deployment methodallows for accurate placement of the device 40 within the uterine cavity44, as shown in FIG. 25. In particular, the mesh strips 150 can beplaced adjacent to each other, thereby creating a uniform covering. Thismethod allows the physician to deploy the device 40 to specific areas orsites within the uterus (similar to the method by which carpeting islaid in a room or icing is piped onto a cake).

[0151] In yet another embodiment, shown in FIG. 26, a tweezer-likedevice 152 is used to place the strips of mesh 150 into the uterinecavity. The physician manipulates the tweezer 152 to grab onto one endof a mesh strip 150. With the catheter 96 properly positionedtranscervically within the patient's uterus, the tweezer 152, togetherwith the mesh strip 150, are inserted into the catheter 96. Thephysician manipulates the tweezer 152 to accurately position the strip150 onto the endometrium. The strip 150 is then released from thetweezer 152 and the process repeated until the uterine cavity is coveredwith strips of mesh 150. As described above, this method is similar to acarpeting-type approach.

[0152] Alternatively, the mesh strips 150 of the carpeting technique canbe configured as continuously deployable strips (not shown). Inparticular, the strips are loaded into the cannula 96 of the deploymenttool such that as each strip is deployed, the next strip isautomatically exposed or positioned for deployment. This technique issimilar to the method by which Kleenex® is automatically dispensed froma tissue dispenser. In addition to mesh strips, the implant 40 can beconfigured as threads/monofilaments 154 loaded with an adhesion creatingsubstance 156. The substance 156 may be a coating, beads or othercomponents adhered to the threads, as shown in FIG. 27.

[0153] In yet another embodiment, the device 40 of the present inventionis comprised of mesh particles. The mesh particles may be created bychopping or grinding the mesh material to a predetermined size. The meshparticles are then loaded into the cannula 96 and deployed as describedabove. This deployment method is similar to the manner by whichinsulation is blown into an attic or other open space. In an alternateembodiment, the mesh particles can be configured as atomizedmicro-particles, semi-rigid foam, suspended aggregate, particulates,powder or other similar forms, including combinations thereof.

[0154] Alternatively, the mesh particles may be suspended in a liquid,gas, foam or other flowable substance that uniformly disperses the meshparticulate when injected by the cannula or catheter 96 into the uterus42. Preferably, the flowable substance is biocompatible and capable ofbeing absorbed by the body. When configured in a liquid or semi-liquidform, the device 40 is dispensed and spread within the uterus 42 using asyringe, instead of a stylet, and a fluid-dispensing catheter 96. Asshown in FIGS. 28A-28C, the catheter includes a cannula or lumen 158capable of dispersing fluid in the uterus 42 via one or more holes/portslocated in the cannula 158. The dispensing cannula 158 may be configuredin the form of a bend, curve, pig-tail, open-loop, closed-loop or othersimilar configuration. In addition, the cannula 158 may also be designedto advance beyond the distal end of the catheter 96 during thedeployment procedure and retract into the catheter at the conclusion ofthe procedure. The curved, distal end of the cannula 158 may be flexibleso that it straightens as it is retracted into the catheter 96. Further,a guide-wire (not shown) may also be formed within the cannula 158 tosteer and/or guide the cannula 158 within the uterus 42 of the patient.

[0155] In one embodiment, the particular composition or material make-upof the flowable substance is such that its viscosity can be modifiedthrough thermal changes. The thermal changes may include those producedexternally or generated by the patient's own body temperature. Oneexample of a thermally-sensitive material is a polymer substance.However, it should be noted that other thermally-sensitive materials notspecifically disclosed, but well known in the art, may also be used withthe present invention.

[0156] In an alternate embodiment, the adhesion forming material isencapsulated in a hydrophillic membrane, elastomeric compound, agelatin, or other similar dissolvable material. Referring to FIG. 29,one or more capsules 162 are placed in the uterus 42 of the patientusing a catheter, cannula or other type of dispensing device 96. Astylet (not shown) may be used to push and position the capsule(s) 162in the uterine cavity. Contact with the uterine tissue causes themembrane of the capsule 162 to dissolve and, thereby, deploy theencapsulated material. Alternatively, the capsule 162 could be irrigatedwith a separate solution dispensed from the catheter 96 to acceleratethe dissolution process. The encapsulated material may be aself-expanding or self-spreading material, such as a liquid, gel, foam,shaped-foam or other similar material. The self-expanding material maybe absorbed by the tissues during adhesion formation. Alternatively, theself-expanding material may be non-absorbable and, thereby, forms thescaffolding or structure for tissue in-growth and subsequent adhesionformation.

[0157] In an alternate embodiment, shown in FIGS. 30A and 30B, thedeployment tool comprises a para-tube 164 housed within a catheter 96and a funnel 166. The funnel 166 functions to dilate the cervix andsplit the para-tube 164 into a fan-shaped configuration as it isadvanced through the funnel 166 and into the uterus 42 of the patient.The expanded structure of the para-tube 164 dispenses the fluid, gas orfoam-type implant 40 throughout the uterine cavity. After the implant 40is dispensed within the uterus 42, the para-tubes 164 are retracted backinto the catheter 96 and the tool is removed from the patient. Referringto FIG. 30C, in another embodiment, hooks 168 located on the distal endof the para-tubes 164 can be used to catch or grab onto the mesh of theimplant 40 and spread the device 40 within the cavity of the uterus 42.The retraction and removal methods are similar to those previouslydescribed.

[0158] After insertion of the device 40 is completed, a vacuum can beapplied to the uterine cavity via the cervical canal. Alternatively, theimplant or device 40 itself may also have a filtering component(compatible with the uterine tissue) integrated into the device 40 thatpermits the evacuation of air via a vacuum applied to the filteringcomponent. As such, a mating device is attached to the cannula96/filtering component and is used to create a seal on the cervix 50.Applying a light vacuum via the mating device produces the seal. Thevacuum helps the surrounding uterine tissue make better contact with theinserted device 40 and, thereby, assists in luminal bridging or adhesioncreation between the uterine surfaces. The length of time that thevacuum is applied to the uterine cavity is dependent upon the conditionof the patient and the procedure being performed; however, vacuum isgenerally applied for a time period of several minutes.

[0159] A plug or cap, similar to those previously described, may beinserted into or placed over the cervix to also help contain the device40. The cap prevents movement of the device 40 or migration of thematerial, especially when the material is in a liquid configuration. Thecap may be made of a material that, over a period of time, is absorbedby the surrounding tissue. This configuration of the cap eliminates theneed to remove the cap at a later time and/or during a secondaryprocedure.

[0160] An additional tool or device may also be used in conjunction withthe device of the present invention. Referring to FIGS. 31A and 31B, thetool comprises a cannula, catheter or lumen-based device 170 havinggraduated indicators or markings 172 along the length of the device 170.During use, the distal end 174 of the tool 170 is inserted into thevagina 176 of the patient. When the tip of the catheter 170 reaches thecervical opening 178, the catheter marking visible at the location ofthe vaginal opening (i.e. reference point 1) is noted by thephysician/user. The catheter 170 is further inserted through the cervixand into the uterus 42 of the patient until it abuts the rear wallfundus 180 of the uterus 42. When the tip of the catheter 170 abuts therear wall 180 of the uterus 42, the catheter marking visible at thevaginal opening (i.e. reference point 2) is also noted by the physician.As such, the physician would then use the two reference points todetermine the length of the uterus 42 and/or fill volume of the uterinecavity.

[0161] In general, the markings on the device 170 allow the physician todetermine the two points of reference within the filling range of theuterus 42. During use, the physician would begin to dispense thefluid-implant when the catheter 170 was at its maximum depth in theuterus 42. The physician would continue to dispense the fluid-implantand simultaneously retract the catheter 170 until the tip of thecatheter 1.70 reached the minimal depth (indicated by reference point2). In this configuration, the markings act as a guide to give thephysician an understanding of where to fill. Further, the markings mayalso enable the physician to determine the shape of the uterine cavityand the amount of material to dispense (via depth measurements and,possibly, an associated algorithm or chart).

[0162] Marker Technology

[0163] In addition to reducing and/or eliminating menorrhagia, thedevice 40 of the present invention can also be used as a uterine marker.The marker provides the physician with the ability to visualize andquantify any endometrial growth or abnormality, such as endometrialhyperplasia and/or endometrial cancer. In this regard, the marker may beused as an absolute reference from which the physician may gage thedifference of other features (growths or other irregularities). Themarker of the present invention may also be used to assist the physicianin determining the plane or location of view (e.g. determines the depthof the imaging plane) such that the cross-section or outside/insidediameters of the uterus may be determined and compared with subsequentdiagnostic procedures. The marker may also be used by the physician whenperforming a non-invasive biopsy, using the marker as a landmark forguidance to the site under an imaging technique. Therefore, the markeracts as a landmark to assist the physician in determining visual ordimensional differences in the uterus.

[0164] In general, the marker component is biocompatible and stable whenembedded or implanted over long periods of time (i.e. permanently)within tissue formed on the interior of the uterus 42. As such, themarker material should have good dimensional stability and allow forvisualization when imaged using ultrasound, magnetic resonance imaging(MRI), computed tomography (CT), x-ray or other common imagingtechnique, including any combination of such techniques. The marker canbe incorporated into the implant device 40, deployment device, and/orpretreatment device previously described, or can be provided as astand-alone device.

[0165] When combined with or within the implant 40, the marker allowsthe physician to determine placement of the implant 40 (i.e. coverage,position, etc.), both short term and long term, and track/assess changesin the surrounding tissue. In one embodiment, shown in FIG. 32, the meshor other adhesion promoting substance of the device 40 is connected tothe marker 182 (configured as a bead) to ensure that the marker 182remains in a fixed, known location. Referring to FIG. 33, in anotherembodiment of the invention, the marker 182 is suspended in the adhesionpromoting substance 40.

[0166] As referenced above, the marker may be used either as astand-alone device (i.e. diagnostic tool) or in combination with otherprocedures or implants previously described. In general, the stand-alonemarker design would be intended as a diagnostic tool and used onnormal/healthy women for assisting in detection of potentialabnormalities within the uterus (such as fibroids, cancer, or otherabnormalities). The stand-alone marker device may vary in size from thatof an IUD to a bead as small as 0.04 inch (0.1 cm) in diameter. Ingeneral, the marker device should be small enough to allow it to passthrough the catheter or deployment device and be imaged via ultrasoundor other means. Further, the size and/or shape of the marker device mayalso be adjustable to allow the marker to conform to the configurationof the uterus. Therefore, the size of the marker device may either beselected to correspond to one of a predetermined range of uterus sizesor adjusted at the time of insertion to conform to the patient'sparticular uterus size/shape.

[0167] In another embodiment of the invention, the marker may be acomponent that is used to hold the device/implant in place, therebyacting as an anchor point. The marker may be anchored to the walls orfundus of the uterus to maintain its position and minimize thepossibility for expulsion. The marker may be delivered with a device,such as a catheter or other type of deployment device, that allows forattachment of the marker to the uterine walls. Alternatively, the markercould also be a feature of the implant 40 and delivered via an implantdeployment tool/device.

[0168] The ideal marker allows for imaging to be performed at any angleand the marker to always be viewed at true length. An example of such adesign is a marker with a spherical shape. Alternatively, a hollow,equilateral triangular shape or design may also be used. In thisconfiguration, the viewing angle is in true position when all sides ofthe triangle are of equal length. However, numerous other shapes mayalso be used to image both two-dimensional and three-dimensional views.Examples of applicable marker shapes or designs include sphere, tube,donut, hollow sphere, curved object or any other geometric shape of aknown size.

[0169] In addition, the marker may consist of a series of spacedspheres/markers to provide the physician with a multiple number of nodesor test sights to measure the thickness of the myometrium, endometrium,or other desired tissue or site. The multiple markers may be equallyspaced or spaced at intervals that are critical points of measurement.Further, the multiple markers may be the same shape/size or differentshapes/sizes to differentiate between the individual markers. Thephysician will be able to know which marker the measurements are takenat to create a repeatable measurement at each site that can be monitoredduring check-ups.

[0170] As previously described, the marker is externally imaged usingany of the above-mentioned techniques. For example, the ultrasound andx-ray based imaging techniques rely on different material densities fordetection and/or imaging. Accordingly, the marker should have a densitythat is different from the density of the surrounding tissue. Thedensity difference allows for the imaging device to precisely indicatethe location of the marker and its relative distance to various featureswithin the uterus, myometrium, cervix, etc. As such, the greater thedensity difference, the greater the image intensity.

[0171] A very broad range of materials may be used for the marker, sinceany material that has a density different from water (i.e. tissue) wouldbe acceptable. Examples of these materials include, but are not limitedto, polypropylene, ethylene, titanium, urethane, nylon, GORE-TEX®, PTFE,Nitinol®, stainless steel, proteins, or any type of biological materialthat is stabile (not resorbed or absorbed by the body; i.e. bone, teeth,etc.). In addition, the marker may be configured as either a solid orhollow component.

[0172] Surface finish of the marker may also be an important feature forvisibility/imaging and tissue growth into the marker. For example, arough surface finish is more readily viewable under ultrasound due tothe defraction/deflection of sound waves. In addition, a markerconfigured with surface barbs or undercuts not only securely affixes themarker to the uterine tissue but also may promote tissue in-growth.Thus, overall device structure and material composition may enhance bothimaging and in-growth of surrounding tissue into the marker.

[0173] Although only one marker is required, multiple markers may alsobe used. In particular, multiple markers may have the added benefit ofallowing for more exact measurement or better visualization, dependingon the placement of the marker to the area of interest.

[0174] In another embodiment of the invention, the marker may be made ofa combination of materials to allow for multiple imaging modes. Forexample, the marker material may be a polymeric substance with metallicssuspended in the resin. This configuration gives the marker combinedpolymeric and metallic characteristics which allow imaging of the markerin numerous formats. Alternatively, the marker may also be a hollowmember that is filled with a liquid (for example, a drug) or gas capableof permeating the hollow member. The hollow member is then imaged todetermine the amount of drug released and, thereby, act as a marker. Inan alternate embodiment, after all of the liquid is diffused, the hollowmember can be refilled using a syringe. This refilling technique wouldbe similar to those used with subcutaneous access devices used in the IVdrug dispensing industry.

[0175] In another embodiment of the invention, the marker comprises oneor more coatings applied to the implant/device 40. Examples of such adevice include a dyed mesh or coated ball. In addition, the coating maybe dissolvable, thereby permitting the coated device to be initiallyimaged using one type of imaging technique and, after the coating iscompletely dissolved, imaged using an alternate, long-term imagingtechnique. One example of this type of marker configuration is a polymerbead coated with radiopaque ink that is water-soluble. The bead isinitially imaged using x-ray fluoroscopy. After the ink is dissolved(generally within one to three days), the bead may be subsequentlyimaged using ultrasound. Further, the ink may be designed to dissolvedue to the in-growth or formation of tissue on the marker. This wouldenable the physician to accurately determine when the adhesion has beensufficiently formed, since the ink/dye would be completely dissolvedwhen the marker is fully surrounded with connective tissue (i.e.adhesions).

[0176] In an alternate embodiment, the marker may be a biologicalmaterial that is reactive to any or specific cancerous cells and/ortissues. The reaction would cause the biological material to change itsproperties (such as density), making it imagable with an ultrasonicdevice or other imaging mechanism. Alternatively, the biologicalmaterial may be a substance coated on the exterior portion of the markerthat prevents liquid/moisture penetration. When the biological materialcontacts specific tissues/cells, the resulting reaction causes theprotective coating to become porous. As the porosity increases, imagingcontrast decreases. Thus, when the disease (specific tissues/cells) isin an advanced state, the marker is barely, if at all, imagable. Inanother embodiment, as the porosity increases, bodyfluids/liquid/moisture penetrate into the marker device, causing thephysical structure of the marker to change. For example, the structuremay be distorted, deformed, uniformly expanded in overall size,uniformly reduced in size, randomly expanded in size or randomly reducedin size. The degree of structural change may be used to indicate howadvanced the disease state is.

[0177] Alternatively, the biological material may also cause a specificreaction when cancerous cells are encountered. For example, the reactionmay create a response that promotes secretions through the cervix. Thesecretions could then be detected during patient examination ordiagnosis using an appropriate swab or assay test.

[0178] With the above parameters in mind, one preferred example of auterine marker 182 is shown in FIG. 34, in conjunction with the uterus42. With this one preferred embodiment, the uterine marker 182 consistsof two marker components that are secured to the uterine walls at knownlocations. In this configuration, the uterine marker 182 can be formedinto the delivery material of the implant/device 40 previouslydescribed. Alternatively, the uterine marker 182 can be deployedindependently. Regardless, once in place, the uterine marker 182provides the ability to externally image and, therefore, monitor one ormore specific uterine locations and characteristics, for example thethickness of the endometrial tissue. The uterine marker 182 effectivelyprovides a “baseline” of endometrial tissue thickness. This baselinevalue can be compared to subsequent readings to evaluate and quantifyany changes in the endometrial tissue. For example, with the onepreferred embodiment, the marker components can be initially imaged anda distance between the two components determined (i.e. calculated) andstored. At a later date, a new distance value can be determined byre-imaging the uterus 42, including the uterine markers 182. When achange in distance is found, an early identification of potentialabnormalities is given, such as the formation of cancerous tissue.

[0179] Another example of a uterine marker comprises a bead formed ofimagable material and secured to the endometrial tissue. The bead has aknown diameter or thickness that is viewable by the imaging device.Additionally, the imaging equipment also provides an indication of theendometrial tissue level, typically in the form of different imagedensities (e.g; endometrial tissue appears lighter in contrast than aremainder of the uterine walls). By providing the bead with a knownthickness, a relationship between the observed endometrial tissuethickness and the actual bead diameter/thickness can be made and noted.Subsequent observations/relationships can be noted and compared to thisbaseline measurement. Any changes can provide a preliminary indicationof uterine abnormalities. Additional examples of the uterine markerinclude markers comprising three or more components (such as a T-shapeddevice) to provide an additional spatial orientation of the uterus.

[0180] Regardless of the exact form, the uterine marker greatly aids inthe early detection of uterine cancer or other abnormalities, and offersa major benefit not available with conventional diagnostic techniques orprocedures. With the uterine marker, any physician can easily andquickly evaluate the patient and image and measure the uterine markerlocations and related attributes (such as distances between markercomponents) using conventional imaging equipment.

[0181] Other Applications

[0182] The above disclosed technology may also be used in the veterinaryscience field for treatment of similar disease states within animals.The use of the implant may be particularly beneficial to breeders,especially in treatment of large animals such as horses. Also, thisimplant system may have application in the treatment of similar diseasestates in primates or may be used to study the biology of intrauterineadhesions and its tissue morphology.

[0183] In addition to providing an effective means of treating uterinedisorders, the device and method of use of the present inventioneffectively reduce pain, infections and post operative hospital stays.Further, the various treatment methods also improve the quality of lifefor patients.

[0184] Although the invention has been described in terms of particularembodiments and applications, one of ordinary skill in the art, in lightof this teaching, can generate additional embodiments and modificationswithout departing from the spirit of or exceeding the scope of theclaimed invention. Accordingly, it is to be understood that the drawingsand descriptions herein are proffered by way of example to facilitatecomprehension of the invention and should not be construed to limit thescope thereof.

What is claimed is:
 1. A method of treating the uterus of a femalepatient comprising: introducing an implant into the uterine cavity;positioning said implant in a lower ½ of said uterine cavity; allowingsaid implant to remain in said uterine cavity to cause a tissue responsesufficient to treat said uterus.
 2. A method according to claim 1,wherein said implant is allowed to remain in said uterine cavity atleast until said treatment eliminates menorragia.
 3. A method accordingto claim 1, wherein said implant is allowed to remain in said uterinecavity at least until said treatments causes contraception in saiduterus.
 4. A method according to claim 1, wherein said implant isallowed to remain in said uterine cavity at least until said treatmentcauses the formation of adhesions in said uterus.
 5. A method accordingto claim 1, wherein the introducing of said implant includes introducingan implant having a frame.
 6. A method according to claim 5, wherein thepositioning of said implant includes expanding said frame so as totraverse a wall of said lower Y of said uterine cavity.
 7. A methodaccording to claim 1, wherein the introducing of said implant includesintroducing an implant having a mesh material.
 8. A method according toclaim 7, wherein the introducing of said implant includes introducing animplant having a mesh material comprised of polyester.
 9. An implant fortreating a uterus of a female patient comprising: a substance configuredfor causing a tissue response in uterine tissue; said substance beingsized and shaped for placement in a lower Y of a uterine cavity of saiduterus.
 10. An implant according to claim 9, wherein said substance isconfigured for causing a tissue response that eliminates menorrhagia.11. An implant according to claim 9, wherein said substance isconfigured for causing a tissue response that causes contraception insaid uterus.
 12. An implant according to claim 9, wherein said substanceincludes a frame covered at least in part by a mesh material.
 13. Animplant according to claim 12, wherein said mesh material is a polyestermaterial.
 14. An implant according to claim 12, wherein said frameincludes a plurality of linear extensions.
 15. An implant according toclaim 14, wherein at least two of said linear extensions are extendableto substantially traverse a wall of said uterine cavity.
 16. An implantaccording to claim 12, wherein said frame is collapsible to a sizesufficiently small so as to be retained in a delivery catheter.
 17. Animplant according to claim 1, wherein said substance is sized and shapedto conform to the size and shape of said lower ½ of said uterine cavity.